Abstract
Acclimatization to hypoxia or high altitude involves physiological adaptation processes, to influence oxygen (O2) transport and utilization. Several natural products, including aromatic aldehydes and isothiocyanates stabilize the R-state of hemoglobin (Hb), increasing Hb-O2 affinity and Hb-O2 saturation. These products are a counter intuitive therapeutic strategy to increase O2 delivery during hypoxia. 5-Hydroxymethylfurfural (5-HMF) is well known Amadori compound formed during the Maillard reaction (the non-enzymatic browning and caramelization of carbohydrate-containing foods after thermal treatment), with well documented effects in Hb-O2 affinity. This study explores the therapeutic potential of 5-HMF on left ventricular (LV) cardiac function (LVCF) during hypoxia. Anesthetized Golden Syrian hamsters received 5-HMF i.v., at 100 mg/kg and were subjected to stepwise increased hypoxia (15, 10, and 5%) every 30 min. LVCF was assessed using a closed chest method with a miniaturized conductance catheter via continuous LV pressure-volume (PV) measurements. Heart hypoxic areas were studied using pimonidazole staining. 5-HMF improved cardiac indices, including stroke volume (SV), cardiac output (CO), ejection fraction (EF), and stroke work (SW) compared to the vehicle group. At 5% O2, SV, CO, EF, and SW were increased by 53, 42, 33, and 51% with 5-HMF relative to vehicle. Heart chronotropic activity was not statistically changed, suggesting that differences in LV-CF during hypoxia by 5-HMF were driven by volume dependent effects. Analysis of coronary blood flow and cardiac muscle metabolism suggest no direct pharmacological effects from 5-HMF, therefore these results can be attributed to 5-HMF-dependent increase in Hb-O2 affinity. These studies establish that naturally occurring aromatic aldehydes, such as 5-HMF, produce modification of hemoglobin oxygen affinity with promising therapeutic potential to increase O2 delivery during hypoxic hypoxia.
Highlights
Food products are subjected to thermal treatments to assure microbiological safety, eliminate enzymatic activities, and to obtain desirable sensory properties. 5-Hydroxymethylfurfural (5-HMF) is naturally formed during the thermal treatment of carbohydrate-containing foods because of the Maillard reaction. 5-HMF is known as an Amadori compound, resulting from tautomerization of the N-glycoside of an aldose or the glycosylamine to the corresponding 1-amino-1-deoxy-ketose via an immine intermediate (Hodge, 1955; Kurti and Czako, 2005)
This study aims to evaluate the effect of increased Hb-O2 affinity with 5-HMF in left ventricle (LV) cardiac function (LVCF) during hypoxia
This study exposes that relatively small amount of 5-HMF preserved left ventricular (LV) cardiac function and reduced myocardial hypoxia during severe hypoxic hypoxia (5% O2)
Summary
Food products are subjected to thermal treatments to assure microbiological safety, eliminate enzymatic activities, and to obtain desirable sensory properties. 5-Hydroxymethylfurfural (5-HMF) is naturally formed during the thermal treatment of carbohydrate-containing foods because of the Maillard reaction (non-enzymatic browning or caramelization). 5-HMF is known as an Amadori compound, resulting from tautomerization of the N-glycoside of an aldose or the glycosylamine to the corresponding 1-amino-1-deoxy-ketose via an immine intermediate (Hodge, 1955; Kurti and Czako, 2005). 5-Hydroxymethylfurfural (5-HMF) is naturally formed during the thermal treatment of carbohydrate-containing foods because of the Maillard reaction (non-enzymatic browning or caramelization). 5-HMF generally is known as an indicator of heating for a wide range of foods (Rada-Mendoza et al, 2002). Several factors influence the formation of 5-HMF in foods, including carbohydrate content, pH, temperature of treatment, and water content (Hodge, 1955). Monosaccharides (i.e., fructose or glucose) are substrates for 5-HMF production (Rada-Mendoza et al, 2002). The toxicological relevance of 5-HMF at very high concentrations is minimal (Ulbricht et al, 1984). Recent studies showed that 5-HMF orally, intraperitoneally, or intravenously has a high bioavailability (Abdulmalik et al, 2005). Recent studies showed that 5-HMF orally, intraperitoneally, or intravenously has a high bioavailability (Abdulmalik et al, 2005). 5-HMF has a high red cell membrane permeability, where it increases hemoglobin (Hb) O2 affinity by stabilizing the R-state of Hb, which has higher O2 affinity (Abdulmalik et al, 2005). 5-HMF binds covalently with Hb to form a high-affinity imine Hb adduct in a symmetrical fashion with the NH2-terminal α Valine-1 of Hb, allosterically shifting the Hb-O2 equilibrium curve at relatively low 5-HMF concentrations (Abdulmalik et al, 2005)
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